• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5455-5461
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• 2012

Luteolin is a plant flavonoid which exhibits anti-oxidative, anti-inflammatory and anti-tumor effects. However, the antiproliferative potential of luteolin is not fully understood. In this study, we investigated the effect of luteolin on cell cycling and apoptosis in human esophageal squamous carcinoma cell line Eca109 cells. MTT assays showed that luteolin had obvious cytotoxicity on Eca109 with an $IC_{50}$ of $70.7{\pm}1.72{\mu}M$ at 24h. Luteolin arrested cell cycle progression in the G0/G1 phase and prevented entry into S phase in a dose- and time-dependent manner. as assessed by FCM. Luteolin induced apoptosis of Eca109 cells was demonstrated by AO/EB staining assay and annexin V-FITC/PI staining. Moreover, luteolin downregulated the expression of cyclin D1, survivin and c-myc, and it also upregulated the expression of p53, in line with the fact that luteolin was able to inhibit Eca109 cell proliferation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4469-4475
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• 2012

Background: The potential use of hypomethylation of Long INterspersed Element 1 (LINE-1) and Alu elements (Alu) as a biomarker has been comprehensively assessed in several cancers, including head and neck squamous cell carcinoma (HNSCC). Failure to detect occult metastatic head and neck tumors on radical neck lymph node dissection can affect the therapeutic measures taken. Objective: The aim of this study was to investigate the LINE-1 and Alu methylation status and determine whether it can be applied for detection of occult metastatic tumors in HNSCC cases. Methods: We used the Combine Bisulfite Restriction Analysis (COBRA) technique to analyse LINE-1 and Alu methylation status. In addition to the methylation level, LINE-1 and Alu loci were classified based on the methylation statuses of two CpG dinucleotides in each allele as follows: hypermethylation ($^mC^mC$), hypomethylation ($^uC^uC$), and 2 forms of partial methylation ($^mC^uC$ and $^uC^mC$). Sixty-one lymph nodes were divided into 3 groups: 1) non-metastatic head and neck cancer (NM), 2) histologically negative for tumor cells of cases with metastatic head and neck cancer (LN), and 3) histologically positive for tumor cells (LP). Results: Alu methylation change was not significant. However, LINE-1 methylation of both LN and LP was altered, as demonstrated by the lower LINE-1 methylation levels (p<0.001), higher percentage of $^mC^uC$ (p<0.01), lower percentage of $^uC^mC$ (p<0.001) and higher percentage of $^uC^uC$ (p<0.001). Using receiver operating characteristic (ROC) curve analysis, $%^uC^mC$ and $%^mC^uC$ values revealed a high level of AUC at 0.806 and 0.716, respectively, in distinguishing LN from NM. Conclusion: The LINE-1 methylation changes in LN have the same pattern as that in LP. This epigenomic change may be due to the presence of occult metastatic tumor in LN cases.

• BMB Reports
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• v.47 no.5
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• pp.274-279
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• 2014

Bortezomib has been known as the most promising anti-cancer drug for multiple myeloma (MM). However, recent studies reported that not all MM patients respond to bortezomib. To overcome such a stumbling-block, studies are needed to clarify the mechanisms of bortezomib resistance. In this study, we established a bortezomib-resistant cell line (U266/velR), and explored its biological characteristics. The U266/velR showed reduced sensitivity to bortezomib, and also showed cross-resistance to the chemically unrelated drug thalidomide. U266/velR cells had a higher proportion of CD138 negative subpopulation, known as stem-like feature, compared to parental U266 cells. U266/velR showed relatively less inhibitory effect of prosurvival NF-${\kappa}B$ signaling by bortezomib. Further analysis of RNA microarray identified genes related to ubiquitination that were differentially regulated in U266/velR. Moreover, the expression level of CD52 in U266 cells was associated with bortezomib response. Our findings provide the basis for developing therapeutic strategies in bortezomib-resistant relapsed and refractory MM patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6991-6996
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• 2015

In the past decade, the incidence and mortality rates of cholangiocarcinoma (CCA) have been increasing worldwide. The relatively low responsiveness of CCA to conventional chemotherapy leads to poor overall survival. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has emerged as the most promising anti-cancer therapeutic agent since it is able to selectively induce apoptosis of tumor cells but not normal cells. In this study, we aimed to investigate the therapeutic effect of TRAIL in CCA cell lines (M213, M214 and KKU100) compared with the immortal biliary cell line, MMNK1, either alone or in combination with a subtoxic dose of 5-fluorouracil (5-FU). We found that recombinant human TRAIL (rhTRAIL) was a potential agent which significantly inhibited cell proliferation and mediated caspase activities (caspases 8, 9 and 3/7) and apoptosis of CCA cells. The combined treatment of rhTRAIL and 5-FU effectively enhanced inhibition of CCA cell growth with a smaller effect on MMNK1. Our finding suggests TRAIL to be a novel anti-cancer therapeutic agent and advantage of its combination with a conventional chemotherapeutic drug for effective treatment of CCA.

• Journal of Microbiology and Biotechnology
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• v.11 no.5
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• pp.876-879
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• 2001

${\gamma}$ -Tubulin is an essential component involved in microtubule nucleation. The present work examined whether the fast proliferation of cancer cells can be retarded by the depletion of ${\gamma}$ -tubulin expression. Two different gastric cancer cell lines and one control cell line were treated with antisence oligonucleotides complementary to the messenger RNA of ${\gamma}$ -tubulin. The$[^3H]$ -thymidine incorporation in the two gastric cancer cell lines, SNU-1 and SNU-216, was dramatically reducd by treatment with the ${\gamma}$ -tubulin antisense oligonucleotides in a dosage-dependent manner. In contrast, the control cell line, NIH/3T3, showed no significant effect from the antisense oligonucleotides even at a high concentration. The ablation of ${\gamma}$ -tubulin expression in the tumor cells resulted in an altered DNA synthesis during mitosis and it decreased the cell progression. Accordingly, the use of antisense oligonucleotides may be an effective way of inhibiting the proliferation of human gastric cancers.

• The Korea Journal of Herbology
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• v.28 no.5
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• pp.39-44
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• 2013

Objectives : Allergy is an immune dysfunction caused by degranulation from mast cells in the early phase of allergic disease. The purpose of this study was to investigate the anti-allergic effect of fermented Angelicae gigantis Radix in human mast cell line, HMC-1. Method : The Angelicae gigantis Radix was fermented by Lactobacillus acidophilus. The cell toxicity of fermented Angelicae gigantis Radix(FAGR) was determined by MTT assay. The release of ${\beta}$-hexosaminidase from HMC-1 stimulated by phorbol-12-myristate 13-acetate (PMA) plus A23187 was determined by ${\beta}$-hexosaminidase assay. Also, the concentrations of cytokines (interleukin-$1{\beta}$, -6, -8 and tumor necrosis factor-alpha) were measured by enzyme-linked immunosorbent assay. The gene expression of COX-2 from HMC-1 stimulated by phorbol-12-myristate 13-acetate (PMA) plus A23187 was determined by reverse transcription polymerase chain reaction. The release of histamine on substance P-stimulated HMC-1 was measured by histamine assay. Result : The FAGR suppressed the release of ${\beta}$-hexosaminidase, a marker of degranulation, from HMC-1 stimulated by PMA plus A23187. The FAGR inhibited the production of interleukin-$1{\beta}$, -6, -8 and tumor necrosis factor-alpha. The FAGR inhibited the expression of COX-2 mRNA. The FAGR suppressed the release of histamine on substance P-stimulated HMC-1. Conclusion : These results provide that FAGR may be beneficial in the treatment of allergic inflammatory disease.

• Journal of Microbiology
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• v.37 no.2
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• pp.111-116
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• 1999

Tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2) is known to act as a signal transducer that connects TNFR2 to its downstream effector functions such as proliferation of thymocytes, regulation of gene expression, and cell death. TRAF2 consists of largely two domains, the N-terminal half that contains a signal-emanating region and the C-terminal half that is responsible for binding to the intracellular region of TNFR2. In this study, we examined the possible roles of TRAF2 in granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression and cell death. A truncated mutant of TRAF2 ( 2-263) that contains only a C-terminal half was generated, and transiently transfected to the A549 cell, a human lung cancer cell line, and L929 cell, a murine TNF-sensitive cell line. GM-CSF mRNA was induced in untransfected A540 cells both in dose- and time-dependent manner upon the exposure of TNF. However, neither the full length TRAF2 nor the mutant altered GM-CSF mRNA production regardless of the presence or absence of TNF. Furthermore, neither TRAF2 versions significantly changed the cytotoxic effect of TNF on L929 cells. These data suggest that TRAF2 may not be involved in the signal transduction pathway for GM-CSF gene induction and cell death mediated by TNF.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2859-2863
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• 2013

Polyphenolic compounds from pomegranate fruit extracts (PFEs) have been reported to possess antiproliferative, pro-apoptotic, anti-inflammatory and anti-invasion effects in prostate and other cancers. However, the mechanisms responsible for the inhibition of cancer invasion remain to be clarified. In the present study, we investigated anti-invasive effects of ellagic acid (EA) in androgen-independent human (PC-3) and rat (PLS10) prostate cancer cell lines in vitro. The results indicated that non-toxic concentrations of EA significantly inhibited the motility and invasion of cells examined in migration and invasion assays. The EA treatment slightly decreased secretion of matrix metalloproteinase (MMP)-2 but not MMP-9 from both cell lines. We further found that EA significantly reduced proteolytic activity of collagenase/gelatinase secreted from the PLS-10 cell line. Collagenase IV activity was also concentration-dependently inhibited by EA. These results demonstrated that EA has an ability to inhibit invasive potential of prostate cancer cells through action on protease activity.

• Korean Journal of Pharmacognosy
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• v.29 no.3
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• pp.243-247
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• 1998

A diverse panel of human tumor cell lines and a mouse melanoma cell line (B16-F1) were used for the cytotoxicity test of the nine sesquiterpene lactones with ${\beta}-methylene-{\gamma}-lactone$ group isolated from Hemisteptia lyrata, Chrysanthemum zawadskii and Chrysanthemum boreale. In the cell adhesion inhibitory activity test against B16-F1 mouse melanoma cell, hemistepcin B, cumambrin B, costunolide and tulipinolide were shown significant activities with $IC_{50}$ range of 2.2, 4.1, 0.9 and $0.3\;{\mu}g/ml$, respectively. In the cytotoxicity test against human tumor cells, the most active compound was costunolide having $IC_{50}$ values of below $0.3\;{\mu}g/ml$ against all the tested cell lines except for UACC62. Cumambrin A, hendelin and costunolide exhibited more strong activity against HCT15 and UO-31 cell lines than a positive control, adriamycin. All tested compounds showed an $IC_{50}$ values of below $5.0\;{\mu}g/ml$ against all the tested cell lines.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1353-1365
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• 1997

Background : Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on its potent anti-tumor activity. However, since the efficiency of current techniques of gene transfer is not satisfactory, the majority of current protocols is aiming the in vitro gene transfer to cancer cells and re-introducing genetically modified cancer cells to host. In the previous study, it was shown that TNF-sensitive cancer cells transfected with TNF-$\alpha$ cDNA would become highly resistant to TNF, and the probability was shown that the acquired resistance to TNF might be associated with synthesis of some protective protein. Understanding the mechanisms of TNF -resistance in TNF-$\alpha$ cDNA transfected cancer cells would be. an important step for improving the efficacy of cancer gene therapy as well as for better understandings of tumor biology. This study was designed to evaluate the role of MnSOD, an antioxidant enzyme, in the acquired resistance to TNF of TNF-$\alpha$ cDN A transfected cancer cells. Method : We transfected TNF-$\alpha$ c-DNA to WEHI164(murine fibrosarcoma cell line), NCI-H2058(human mesothelioma cell line), A549(human non-small cell lung cancer cell line), ME180(human cervix cancer cell line) cells using retroviral vector(pLT12SN(TNF)) and confirm the expression of TNF with PCR, ELISA, MIT assay. Then we determined the TNF resistance of TNF-$\alpha$ cDNA transfected cells(WEHI164-TNF, NCIH2058-TNF, A549-TNF, ME180-TNF) and the changes of MnSOD mRNA expressions with Northern blot analysis. Results : The MnSOD mRNA expressions of parental cells and genetically modified cells of WEHI164 and ME180 cells(both are naturally TNF sensitive) were not significantly different The MnSOD mRNA expressions of genetically modified cells of NCI-H2058 and A549(both are naturally TNF resistant) were higher than those of the parental cells, while those of parental cells with exogenous TNF were also elevated. Conclusion : The acquired resistance to TNF after TNF-$\alpha$ cDNA transfection may not be associated with the change in the MnSOD expression, but the difference in natural TNF sensitivity of each cell may be associated with the level of the MnSOD expression.